This invention relates to novel tricyclic aromatic compounds which correspond to the B, C, and D ring skeleton of steroids and which can be used as intermediates for the total synthesis of steroids.
Reported synthesis of the B, C, and D ring skeleton of steroids include those of Joly et al (U.S. Pat. No. 3,274,233) by reaction between a 2-cyano-2-lower alkyl-6-methoxytetralone-1 and a di(lower alkyl)succinate to produce a lower alkyl ester of 1-oxo-8-lower alkyl-4,5-(4'-methoxybenzo)-.DELTA..sup.3(9) -hydrindene-3-carboxylic acid ##STR2##
A synthesis reported by Nomine et al (U.S. Pat. No. 3,115,507) requires conversion of 6-methoxy-3,4-dihydronaphthyl-(2,1)-isoxazole by reaction with an alkyl halide to a 2-alkyl-2-cyano-6-methoxytetralone-1 which is condensed with a dialkyl succinate to give 5-methoxy-13.beta.-substituted-15-alkoxycarbonyl-.DELTA..sup.5,7,9,14 -des-A-gonatetraene-17-one ##STR3##
It is apparent from the foregoing that there is a continuing need for routes to the B, C, and D ring skeleton of steroids which are convenient, which use commercially available inexpensive starting materials and which give high yields of tricyclic aromatic steroid intermediates. Also, in view of depletion of natural sources of intermediates for the total synthesis of steroid drugs, the development of totally synthetic routes is of increasing importance.
Condensation of glyoxal with dimethyl 3-ketoglutarate in aqueous solution buffered to pH 6.0 to a hexacarbomethoxy compound ##STR4## and conversion to a tetracyclic aldol was reported by K. C. Rice et al, Tetrahedron Letters, No. 44, 3767 (1975).
It has been found, in accordance with this invention, that a series of reactions, starting from the foregoing hexacarboalkoxy compound, are extremely simple and convenient, requiring no chromatographic separation steps and provide valuable B, C, D ring precursors of steroidal estrogens and antifertility drugs.